Synthesis, biological activity, pharmacokinetic properties and molecular modelling studies of novel 1H,3H-oxazolo[3,4-a]benzimidazoles: non-nucleoside HIV-1 reverse transcriptase inhibitors

Antivir Chem Chemother. 2001 May;12(3):169-74. doi: 10.1177/095632020101200304.


New 1H,3H-oxazolo[3,4-albenzimidazoles (OBZs) were synthesized as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTI) to extend the structure-activity relationships observed for an early series of related 1H,3H-thiazolo[3,4-a]benzimidazole derivatives (TBZs). The new compounds showed inhibitory activity against the replication of various HIV-1 strains, including NNRTI-resistant strains. Testing of a representative OBZ derivative in an HPLC assay on biological fluids, indicated that the sulphur substitution appreciably improved the metabolic stability of the TBZ compound. In addition, molecular modelling studies demonstrated that OBZs, TBZs and other NNRTIs have similar structural properties, that is a butterfly-like conformation, which is a key structural requirement for reverse transcriptase inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzimidazoles / blood
  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / pharmacology
  • Cell Line
  • Chromatography, High Pressure Liquid
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • HIV-1 / physiology
  • Humans
  • Inhibitory Concentration 50
  • Models, Molecular
  • Oxazoles / blood
  • Oxazoles / chemical synthesis*
  • Oxazoles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Inhibitors / blood
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / pharmacology
  • Structure-Activity Relationship
  • Virus Replication / drug effects


  • 1-(2,6-difluorophenyl)-1H,3H-oxazolo(3,4-a)benzimidazole
  • 1-(2-chloro-6-fluorophenyl)-1H,3H-oxazolo(3,4-a)benzimidazole
  • 1-phenyl-1H,3H-oxazolo(3,4-a)benzimidazole
  • Benzimidazoles
  • Oxazoles
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase